The Brain-Penetrant Pan ErbB Inhibitor Poziotinib Effectively Targets HER2+ Breast Cancer Brain Metastases.

Brain metastasis occurs in about 50% of all women with metastatic HER2+ breast cancer and confers poor prognosis for patients. Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with trastuzumab and HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM). The scarcity of suitable patient-derived in vivo models for HER2+ BCBM has curtailed the study of molecular mechanisms that promote growth and therapeutic resistance in brain metastasis.

The current state of wearable device use in Parkinson's disease: a survey of individuals with Parkinson's.

Background: Interest in wearable device use in Parkinson's disease (PD) has grown rapidly with many compelling studies supporting diagnostic and therapeutic uses. Concurrently, consumer devices have proliferated and their role in health and wellness has expanded. However, incorporation of consumer and medical wearable devices into medical care has in our experience been limited.

A Zr-based metal-organic framework drug release system with long-lasting antibacterial behavior for accelerating wound healing.

Although various antibacterial strategies have been developed, antibiotic chemotherapy remains the primary clinical treatment for bacterial infections. To address the limitations associated with the traditional antibiotic therapy, like burst drug release, rapid drug clearance, and the emergence of drug resistance, it is highly desirable to develop drug release systems that can realize controlled and sustained drug release to enhance the therapeutic efficacy. Herein, we present a novel drug release system, CIP@SU-102, which shows superior and long-lasting antibacterial activity.

Clinicopathologic Characterization of 2 Individuals With Variants-1 Novel Splice Variant, 2 Proteinopathies: A Case Series.

Objectives: Here, we report detailed clinicopathologic evaluation of 2 individuals with pathogenic variants in , including one novel likely pathogenic splice variant. We describe the striking diversity of clinical phenotypes among family members and also the brain and spinal cord neuropathology associated with these 2 distinct variants.

Methods: Two individuals with pathogenic variants in and their families were clinically characterized, and the probands subsequently underwent extensive postmortem neuropathologic examination of their brains and spinal cords.

Therapeutic efficacy of platelet-rich plasma in the management of rib fractures.

Background: This study aimed to investigate the therapeutic efficacy of platelet-rich plasma (PRP) therapy in patients with rib fractures.

Methods: This study retrospectively collected data from patients with acute rib fractures at Ming-Sheng General Hospital from 2020 to 2022 and excluded those who underwent surgical intervention or with severe extrathoracic injuries. PRP was extracted using the patient's blood and injected via ultrasound guidance near the fracture site.

Fibroblast expression of transmembrane protein smoothened governs microenvironment characteristics after acute kidney injury.

The smoothened (Smo) receptor facilitates hedgehog signaling between kidney fibroblasts and tubules during acute kidney injury (AKI). Tubule-derived hedgehog is protective in AKI, but the role of fibroblast-selective Smo is unclear. Here, we report that Smo-specific ablation in fibroblasts reduced tubular cell apoptosis and inflammation, enhanced perivascular mesenchymal cell activities, and preserved kidney function after AKI.

Prophylactic treatment with the c-Abl inhibitor, neurotinib, diminishes neuronal damage and the convulsive state in pilocarpine-induced mice.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival.

Proteome characterization of liver-kidney comorbidity after microbial sepsis.

Sepsis is a life-threatening condition that occurs when the body responds to an infection but subsequently triggers widespread inflammation and impaired blood flow. These pathologic responses can rapidly cause multiple organ dysfunction or failure either one by one or simultaneously. The fundamental common mechanisms involved in sepsis-induced multiple organ dysfunction remain unclear.

Overcoming brain-derived therapeutic resistance in HER2+ breast cancer brain metastasis.

Brain metastasis of HER2+ breast cancer occurs in about 50% of all women with metastatic HER2+ breast cancer and confers poor prognosis for patients. Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with Trastuzumab +/-HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM). The scarcity of suitable patient-derived in-vivo models for HER2+ BCBM has compromised the study of molecular mechanisms that promote growth and therapeutic resistance in brain metastasis.

Synthesis of Upper-Rim Sulfanylpropyl- and Methoxyphenylazo-Substituted Calix[4]arenes as Chromogenic Sensors for Hg and Ag Ions.

A series of calix[4]arenes with upper-rim sulfanylpropyl and -methoxyphenylazo groups (compounds -) were synthesized and found to be effective chromogenic sensors for selectively detecting Hg, Hg, and Ag ions among 18 screened metal perchlorates. In comparison to previously reported diallyl- and dithioacetoxypropyl-substituted calix[4]arenes (, , , , and ) and the newly synthesized compound , the distal (5,17)-disulfanylpropyl-substituted di--methoxyphenylazocalix[4]arene demonstrated superior performance with a limit of detection of 0.028 μM for Hg ions in a chloroform/methanol (v/v = 399/1) cosolvent.

A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness.

Background: For almost a century, it has been recognized that influenza A virus (IAV) infection can promote the development of secondary bacterial infections (SBI) mainly caused by Streptococcus pneumoniae (Spn). Recent observations have shown that IAV is able to directly bind to the surface of Spn. To gain a foundational understanding of how direct IAV-Spn interaction alters bacterial biological fitness we employed combinatorial multiomic and molecular approaches.

NETome: A model to Decode the Human Genome and Proteome of Neutrophil Extracellular Traps.

Neutrophils are the most abundant type of white blood cells in humans with biological roles relevant to inflammation, and fighting off infections. Neutrophil Extracellular Traps (NETs) act as enxogenous agents controlling invasion by bacteria, viruses, fungi, metabolic, and traumatic agents. Traditionally, studies have focused on elucidating molecular and cellular pathways preceding NET formation.

Discovery and Optimization of Pyrrolopyrimidine Derivatives as Selective Disruptors of the Perinucleolar Compartment, a Marker of Tumor Progression toward Metastasis.

The perinucleolar compartment (PNC) is a dynamic subnuclear body found at the periphery of the nucleolus. The PNC is enriched with RNA transcripts and RNA-binding proteins, reflecting different states of genome organization. PNC prevalence positively correlates with cancer progression and metastatic capacity, making it a useful marker for metastatic cancer progression.

The Feasibility of a Machine Learning Approach in Predicting Successful Ventilator Mode Shifting for Adult Patients in the Medical Intensive Care Unit.

: Traditional assessment of the readiness for the weaning from the mechanical ventilator (MV) needs respiratory parameters in a spontaneous breath. Exempted from the MV disconnecting and manual measurements of weaning parameters, a prediction model based on parameters from MV and electronic medical records (EMRs) may help the assessment before spontaneous breath trials. The study aimed to develop prediction models using machine learning techniques with parameters from the ventilator and EMRs for predicting successful ventilator mode shifting in the medical intensive care unit.

Pandemic Influenza Infection Promotes Streptococcus pneumoniae Infiltration, Necrotic Damage, and Proteomic Remodeling in the Heart.

For over a century, it has been reported that primary influenza infection promotes the development of a lethal form of bacterial pulmonary disease. More recently, pneumonia events caused by both viruses and bacteria have been directly associated with cardiac damage. Importantly, it is not known whether viral-bacterial synergy extends to extrapulmonary organs such as the heart.

Kinetic Multi-omic Analysis of Responses to SARS-CoV-2 Infection in a Model of Severe COVID-19.

The host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is poorly understood due to a lack of an animal model that recapitulates severe human disease. Here, we report a Syrian hamster model that develops progressive lethal pulmonary disease that closely mimics severe coronavirus disease 2019 (COVID-19). We evaluated host responses using a multi-omic, multiorgan approach to define proteome, phosphoproteome, and transcriptome changes.

Urethral Catheter Biofilms Reveal Plasticity in Bacterial Composition and Metabolism and Withstand Host Immune Defenses in Hypoxic Environment.

Biofilms composed of multiple microorganisms colonize the surfaces of indwelling urethral catheters that are used serially by neurogenic bladder patients and cause chronic infections. Well-adapted pathogens in this niche are , and spp., species that cycle through adhesion and multilayered cell growth, trigger host immune responses, are starved off nutrients, and then disperse.

Streptococcus pneumoniae Binds to Host Lactate Dehydrogenase via PspA and PspC To Enhance Virulence.

Pneumococcal surface protein A (PspA) and pneumococcal surface protein C (PspC, also called CbpA) are major virulence factors of (). These surface-exposed choline-binding proteins (CBPs) function independently to inhibit opsonization, neutralize antimicrobial factors, or serve as adhesins. PspA and PspC both carry a proline-rich domain (PRD) whose role, other than serving as a flexible connector between the N-terminal and C-terminal domains, was up to this point unknown.

Influenza Causes MLKL-Driven Cardiac Proteome Remodeling During Convalescence.

Rationale: Patients with and without cardiovascular diseases have been shown to be at risk of influenza-mediated cardiac complications. Recent clinical reports support the notion of a direct link between laboratory-confirmed influenza virus infections and adverse cardiac events.

Objective: Define the molecular mechanisms underlying influenza virus-induced cardiac pathogenesis after resolution of pulmonary infection and the role of necroptosis in this process.

Lab-on-a-Filter Techniques for Economical, Effective, and Flexible Proteome Analysis.

Effective and reliable protease digestion of biological samples is critical to the success in bottom-up proteomics analysis. Various filter-based approaches using different types of membranes have been developed in the past several years and largely implemented in sample preparations for modern proteomics. However, these approaches rely heavily on commercial filter products, which are not only costly but also limited in membrane options.

The precaution strategy toward the COVID-19 pandemic in the operating room of a tertiary hospital in Taiwan.

Background: The pandemic of SARS-CoV-2 (COVID-19), which began in December 2019, spread mostly from person to person through respiratory droplets. A recommendation was issued to postpone all elective surgical practices. However, some confirmed or suspected COVID-19 patients required life-saving emergent surgeries.

Oral Microbial Species and Virulence Factors Associated with Oral Squamous Cell Carcinoma.

The human microbiome has been the focus of numerous research efforts to elucidate the pathogenesis of human diseases including cancer. Oral cancer mortality is high when compared with other cancers, as diagnosis often occurs during late stages. Its prevalence has increased in the USA over the past decade and accounts for over 40,000 new cancer patients each year.